Brain-derived neurotrophic factor antisense oligonucleotide impairs memory retention and inhibits long-term potentiation in rats.
We have examined the relationship between brain-derived neurotrophic factor gene expression in the hippocampus and memory retention as well as long-term potentiation of rats. One-way inhibitory avoidance learning was adopted as the behavioural paradigm. Results revealed that brain-derived neurotrophic factor messenger RNA levels in the dentate gyrus of the hippocampus were markedly increased at 1 h, 3 h and 6 h post-training in rats showing good retention performance when compared with the poor retention controls. Direct injection of brain-derived neurotrophic factor antisense oligonucleotide into the dentate gyrus of the hippocampus before memory consolidation takes place markedly impaired retention performance in rats. It also significantly decreased brain-derived neurotrophic factor messenger RNA level in the dentate gyrus. The same antisense treatment also markedly reduced the amplitude and slope of excitatory postsynaptic potential as well as the brain-derived neurotrophic factor messenger RNA level in the dentate gyrus. These results suggest that hippocampal brain-derived neurotrophic factor gene expression plays an important role in the memory consolidation process and in the expression of long-term potentiation in rats. These results provide the first evidence to relate brain-derived neurotrophic factor gene expression and memory function in vertebrates. It further suggests that brain-derived neurotrophic factor gene expression is involved in behavioural plasticity.
Ma
Y L
YL
Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Wang
H L
HL
Wu
H C
HC
Wei
C L
CL
Lee
E H
EH
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics*; D004558:Electric Stimulation; D004594:Electrophysiology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000096:biosynthesis; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D007041:Hypoxanthine Phosphoribosyltransferase